Amanda Pires - Academia.edu (original) (raw)
Papers by Amanda Pires
American Journal of Pathology, 2009
Eosinophils are multifunctional leukocytes implicated in numerous inflammatory diseases. The pres... more Eosinophils are multifunctional leukocytes implicated in numerous inflammatory diseases. The present study was conducted to clarify the precise role of eosinophils in the development of colitis by using eosinophil-depleted mice and a novel chemokine-binding protein that neutralizes CCL11 action. Colitis was induced by administration of dextran sodium sulfate (DSS) to wild-type and eosinophil-deficient ⌬dblGATA-1 mice. Accumulation of eosinophils in the gut of mice given DSS paralleled worsening of clinical score and weight loss. In response to DSS, ⌬dblGATA-1 mice showed virtual absence of eosinophil recruitment, amelioration of clinical score, weight loss, and tissue destruction, and no lethality. There was a decrease in CXCL1 and CCL3 production and decreased neutrophil influx in the intestine of ⌬dblGATA-1 mice. Transfer of bone marrow cells from wild-type mice reconstituted disease manifestation in DSS-treated ⌬dblGATA-1 mice, and levels of CCL11 were increased after DSS treatment and localized to inflammatory cells. Treatment with the chemokine-binding protein evasin-4 at a dose that prevented the function of CCL11 greatly ameliorated clinical score, weight loss, overall tissue destruction, and death rates. In conclusion, the influx of eosinophils is critical for the induction of colitis by DSS. Treatment with a novel chemokine-binding protein decreased eosinophil influx and greatly ameliorated colitis, suggesting that strategies that interfere with the recruitment of eosinophils may be useful as therapy for colitis.
Journal of Clinical Endocrinology & Metabolism, 2007
Background: GH deficiency (GHD) in adults is associated with increased abdominal adiposity and sy... more Background: GH deficiency (GHD) in adults is associated with increased abdominal adiposity and systolic blood pressure, total and low-density lipoprotein cholesterol, and C-reactive protein.
Journal of Periodontology, 2010
Background: This study evaluates the ligature-induced bone loss (BL) and quality of tooth-support... more Background: This study evaluates the ligature-induced bone loss (BL) and quality of tooth-supporting alveolar bone in spontaneously hypertensive rats (SHRs) by histometric, histochemical, and immunohistochemical analyses and assesses the effects of lercanidipine on these parameters.
Chemico-biological Interactions, 2010
The main goal of this work was to investigate the relationship between the effects of three new 1... more The main goal of this work was to investigate the relationship between the effects of three new 1,3,4thiadiazolium mesoionic derivatives on mitochondrial bioenergetics and their previously described chemical structure and antimelanoma activity. The 4-phenyl-5-(2 -Y, 4 -X or 4 -X-cinnamoyl)-1,3,4thiadiazolium-2-phenylamine chlorides differed from each other only in the cinnamoyl ring substituent: MI-J, X = OH; MI-F, X = F; MI-2,4diF X = Y = F. The state 3 respiratory rate was strongly decreased by all derivatives, reaching total inhibition of MI-4F and MI-2,4diF (130 nmol mg −1 protein), when glutamate plus malate were used as substrate. State 3 inhibition was less accentuated with succinate as substrate. Analyses of segments of the respiratory chain indicated complexes I and IV as sites inhibited by the derivatives. State 4 respiration was strongly stimulated by the three derivatives, and was characterized as an uncoupling effect, which was more intense for MI-4F. This stimulus was so pronounced that the values of RCC and ADP/O ratio were only calculated for the lowest concentration (6.5 nmol mg −1 protein). In intact mitochondria, the ATPase activity was increased dramatically by ∼120%, ∼207% and ∼261% for MI-J, MI-4F and MI-2,4diF (32.5 nmol mg −1 protein), respectively.
Chemico-biological Interactions, 2011
The aim of this work was to assess the significance of the interaction of the 1,3,4-thiadiazolium... more The aim of this work was to assess the significance of the interaction of the 1,3,4-thiadiazolium derivatives MI-J, MI-4F and MI-2,4diF with mitochondrial membrane and their effects on energy-linked functions. Mitochondrial swelling in the absence of substrate was inhibited by all derivatives; however, the fluorine derivatives were most effective. MI-4F decreased swelling by ∼32% even at the lowest concentration (65 nmol mg −1 protein), reaching ∼67% at the concentration of 130 nmol mg −1 protein. Swelling of mitochondria in the presence of oxidizable substrates was also strongly decreased by all derivatives. This effect was more pronounced when using glutamate plus malate, and also fluorine derivatives, which promoted complete inhibition at all concentrations (6.5-130 nmol mg −1 protein). Swelling occurred when succinate was the substrate in the presence of MI-J (6.5-65 nmol mg −1 protein); however, the shrinkage rate was strongly decreased. MI-4F and MI-2,4diF also inhibited swelling, with total inhibition occurring at a concentration of 65 nmol mg −1 protein. Lipid peroxidation induced by Fe 3+ -ADP/2-oxoglutarate in isolated mitochondria was inhibited time-and dose-dependently by the derivatives, reaching complete inhibition at the highest concentration (80 nmol mg −1 protein). However, when lipid peroxidation was initiated by peroxyl radicals generated from AAPH, the inhibition was less intense, reaching ∼50%, ∼40% and ∼58% with MI-J, MI-4F and MI-2,4diF (80 nmol mg −1 protein), respectively. The mesoionic compounds also showed superoxide radical scavenging ability of ∼22%, ∼32% and ∼40% (80 nmol mg −1 protein), respectively. Fluorescence polarization experiments showed that the derivatives are able to enter the bilayer, decreasing its fluidity in the hydrophobic DMPC membrane region and ordering the fluid phase. Our results suggest that MI-J, MI-4F and MI-2,4diF interact significantly, albeit in different modes, with mitochondrial membrane, and that fluorine derivatives seem to alter the membrane's properties more markedly. oxygen species; TBA, thiobarbituric acid; TBARS, thiobarbituric acid reactive substances; Tm, midpoint temperature of thermotropic phase transition; Tris, tris(hydroxymethyl)aminomethane.
Cancer Chemotherapy and Pharmacology, 2010
Purpose Nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to reduce cell growth in sev... more Purpose Nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to reduce cell growth in several tumors. Among these possible antineoplastic drugs are cyclooxygenase-2 (COX-2)-selective drugs, such as celecoxib, in which antitumoral mechanisms were evaluated in rats bearing Walker-256 (W256) tumor. Methods W256 carcinosarcoma cells were inoculated subcutaneously (107 cells/rat) in rats submitted to treatment with celecoxib (25 mg kg−1) or vehicle for 14 days. Tumor growth, body-weight gain, and survival data were evaluated. The mechanisms, such as COX-2 expression and activity, oxidative stress, by means of enzymes and lipoperoxidation levels, and apoptosis mediators were also investigated. Results A reduction in tumor growth and an increased weight gain were observed. Celecoxib provided a higher incidence of survival compared with the control group. Cellular effects are probably COX-2 independent, because neither enzyme expression nor its activity, measured by tumoral PGE2, showed significant difference between groups. It is probable that this antitumor action is dependent on an apoptotic way, which has been evaluated by the expression of the antiapoptotic protein Bcl-xL, in addition to the cellular changes observed by electronic microscopy. Celecoxib has also a possible involvement with redox homeostasis, because its administration caused significant changes in the activity of oxidative enzymes, such as catalase and superoxide dismutase. Conclusion These results confirm the antitumor effects of celecoxib in W256 cancer model, contributing to elucidating its antitumoral mechanism and corroborating scientific literature about its effect on other types of cancer.
Chemico-biological Interactions, 2011
Apigenin has been reported to inhibit proliferation of cancer cells; however, the mechanism under... more Apigenin has been reported to inhibit proliferation of cancer cells; however, the mechanism underlying its action is not completely understood. Here, we evaluated the effects of apigenin on the levels of expression and activity of antioxidant enzymes, and the involvement of ROS in the mechanism of cell death induced by apigenin in HepG2 human hepatoma cells. Upon treatment with apigenin, HepG2 cells displayed a reduction in cell viability in a dose-and time-dependent manner, and some morphological changes. In addition, apigenin treatment induced ROS generation and significantly decreased the mRNA levels and activity of catalase and levels of intracellular GSH. On the other hand, apigenin treatment did not alter the expression or activity levels of other antioxidant enzymes. Addition of exogenous catalase significantly reduced the effects of apigenin on HepG2 cell death. We also demonstrated that HepG2 cells are more sensitive to apigenin-mediated cell death than are primary cultures of mouse hepatocytes, suggesting a differential toxic effect of this agent in tumor cells. Our results suggest that apigenin-induced apoptosis in HepG2 cells may be mediated by a H 2 O 2 -dependent pathway via reduction of the antioxidant defenses.
American Journal of Pathology, 2009
Eosinophils are multifunctional leukocytes implicated in numerous inflammatory diseases. The pres... more Eosinophils are multifunctional leukocytes implicated in numerous inflammatory diseases. The present study was conducted to clarify the precise role of eosinophils in the development of colitis by using eosinophil-depleted mice and a novel chemokine-binding protein that neutralizes CCL11 action. Colitis was induced by administration of dextran sodium sulfate (DSS) to wild-type and eosinophil-deficient ⌬dblGATA-1 mice. Accumulation of eosinophils in the gut of mice given DSS paralleled worsening of clinical score and weight loss. In response to DSS, ⌬dblGATA-1 mice showed virtual absence of eosinophil recruitment, amelioration of clinical score, weight loss, and tissue destruction, and no lethality. There was a decrease in CXCL1 and CCL3 production and decreased neutrophil influx in the intestine of ⌬dblGATA-1 mice. Transfer of bone marrow cells from wild-type mice reconstituted disease manifestation in DSS-treated ⌬dblGATA-1 mice, and levels of CCL11 were increased after DSS treatment and localized to inflammatory cells. Treatment with the chemokine-binding protein evasin-4 at a dose that prevented the function of CCL11 greatly ameliorated clinical score, weight loss, overall tissue destruction, and death rates. In conclusion, the influx of eosinophils is critical for the induction of colitis by DSS. Treatment with a novel chemokine-binding protein decreased eosinophil influx and greatly ameliorated colitis, suggesting that strategies that interfere with the recruitment of eosinophils may be useful as therapy for colitis.
Journal of Clinical Endocrinology & Metabolism, 2007
Background: GH deficiency (GHD) in adults is associated with increased abdominal adiposity and sy... more Background: GH deficiency (GHD) in adults is associated with increased abdominal adiposity and systolic blood pressure, total and low-density lipoprotein cholesterol, and C-reactive protein.
Journal of Periodontology, 2010
Background: This study evaluates the ligature-induced bone loss (BL) and quality of tooth-support... more Background: This study evaluates the ligature-induced bone loss (BL) and quality of tooth-supporting alveolar bone in spontaneously hypertensive rats (SHRs) by histometric, histochemical, and immunohistochemical analyses and assesses the effects of lercanidipine on these parameters.
Chemico-biological Interactions, 2010
The main goal of this work was to investigate the relationship between the effects of three new 1... more The main goal of this work was to investigate the relationship between the effects of three new 1,3,4thiadiazolium mesoionic derivatives on mitochondrial bioenergetics and their previously described chemical structure and antimelanoma activity. The 4-phenyl-5-(2 -Y, 4 -X or 4 -X-cinnamoyl)-1,3,4thiadiazolium-2-phenylamine chlorides differed from each other only in the cinnamoyl ring substituent: MI-J, X = OH; MI-F, X = F; MI-2,4diF X = Y = F. The state 3 respiratory rate was strongly decreased by all derivatives, reaching total inhibition of MI-4F and MI-2,4diF (130 nmol mg −1 protein), when glutamate plus malate were used as substrate. State 3 inhibition was less accentuated with succinate as substrate. Analyses of segments of the respiratory chain indicated complexes I and IV as sites inhibited by the derivatives. State 4 respiration was strongly stimulated by the three derivatives, and was characterized as an uncoupling effect, which was more intense for MI-4F. This stimulus was so pronounced that the values of RCC and ADP/O ratio were only calculated for the lowest concentration (6.5 nmol mg −1 protein). In intact mitochondria, the ATPase activity was increased dramatically by ∼120%, ∼207% and ∼261% for MI-J, MI-4F and MI-2,4diF (32.5 nmol mg −1 protein), respectively.
Chemico-biological Interactions, 2011
The aim of this work was to assess the significance of the interaction of the 1,3,4-thiadiazolium... more The aim of this work was to assess the significance of the interaction of the 1,3,4-thiadiazolium derivatives MI-J, MI-4F and MI-2,4diF with mitochondrial membrane and their effects on energy-linked functions. Mitochondrial swelling in the absence of substrate was inhibited by all derivatives; however, the fluorine derivatives were most effective. MI-4F decreased swelling by ∼32% even at the lowest concentration (65 nmol mg −1 protein), reaching ∼67% at the concentration of 130 nmol mg −1 protein. Swelling of mitochondria in the presence of oxidizable substrates was also strongly decreased by all derivatives. This effect was more pronounced when using glutamate plus malate, and also fluorine derivatives, which promoted complete inhibition at all concentrations (6.5-130 nmol mg −1 protein). Swelling occurred when succinate was the substrate in the presence of MI-J (6.5-65 nmol mg −1 protein); however, the shrinkage rate was strongly decreased. MI-4F and MI-2,4diF also inhibited swelling, with total inhibition occurring at a concentration of 65 nmol mg −1 protein. Lipid peroxidation induced by Fe 3+ -ADP/2-oxoglutarate in isolated mitochondria was inhibited time-and dose-dependently by the derivatives, reaching complete inhibition at the highest concentration (80 nmol mg −1 protein). However, when lipid peroxidation was initiated by peroxyl radicals generated from AAPH, the inhibition was less intense, reaching ∼50%, ∼40% and ∼58% with MI-J, MI-4F and MI-2,4diF (80 nmol mg −1 protein), respectively. The mesoionic compounds also showed superoxide radical scavenging ability of ∼22%, ∼32% and ∼40% (80 nmol mg −1 protein), respectively. Fluorescence polarization experiments showed that the derivatives are able to enter the bilayer, decreasing its fluidity in the hydrophobic DMPC membrane region and ordering the fluid phase. Our results suggest that MI-J, MI-4F and MI-2,4diF interact significantly, albeit in different modes, with mitochondrial membrane, and that fluorine derivatives seem to alter the membrane's properties more markedly. oxygen species; TBA, thiobarbituric acid; TBARS, thiobarbituric acid reactive substances; Tm, midpoint temperature of thermotropic phase transition; Tris, tris(hydroxymethyl)aminomethane.
Cancer Chemotherapy and Pharmacology, 2010
Purpose Nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to reduce cell growth in sev... more Purpose Nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to reduce cell growth in several tumors. Among these possible antineoplastic drugs are cyclooxygenase-2 (COX-2)-selective drugs, such as celecoxib, in which antitumoral mechanisms were evaluated in rats bearing Walker-256 (W256) tumor. Methods W256 carcinosarcoma cells were inoculated subcutaneously (107 cells/rat) in rats submitted to treatment with celecoxib (25 mg kg−1) or vehicle for 14 days. Tumor growth, body-weight gain, and survival data were evaluated. The mechanisms, such as COX-2 expression and activity, oxidative stress, by means of enzymes and lipoperoxidation levels, and apoptosis mediators were also investigated. Results A reduction in tumor growth and an increased weight gain were observed. Celecoxib provided a higher incidence of survival compared with the control group. Cellular effects are probably COX-2 independent, because neither enzyme expression nor its activity, measured by tumoral PGE2, showed significant difference between groups. It is probable that this antitumor action is dependent on an apoptotic way, which has been evaluated by the expression of the antiapoptotic protein Bcl-xL, in addition to the cellular changes observed by electronic microscopy. Celecoxib has also a possible involvement with redox homeostasis, because its administration caused significant changes in the activity of oxidative enzymes, such as catalase and superoxide dismutase. Conclusion These results confirm the antitumor effects of celecoxib in W256 cancer model, contributing to elucidating its antitumoral mechanism and corroborating scientific literature about its effect on other types of cancer.
Chemico-biological Interactions, 2011
Apigenin has been reported to inhibit proliferation of cancer cells; however, the mechanism under... more Apigenin has been reported to inhibit proliferation of cancer cells; however, the mechanism underlying its action is not completely understood. Here, we evaluated the effects of apigenin on the levels of expression and activity of antioxidant enzymes, and the involvement of ROS in the mechanism of cell death induced by apigenin in HepG2 human hepatoma cells. Upon treatment with apigenin, HepG2 cells displayed a reduction in cell viability in a dose-and time-dependent manner, and some morphological changes. In addition, apigenin treatment induced ROS generation and significantly decreased the mRNA levels and activity of catalase and levels of intracellular GSH. On the other hand, apigenin treatment did not alter the expression or activity levels of other antioxidant enzymes. Addition of exogenous catalase significantly reduced the effects of apigenin on HepG2 cell death. We also demonstrated that HepG2 cells are more sensitive to apigenin-mediated cell death than are primary cultures of mouse hepatocytes, suggesting a differential toxic effect of this agent in tumor cells. Our results suggest that apigenin-induced apoptosis in HepG2 cells may be mediated by a H 2 O 2 -dependent pathway via reduction of the antioxidant defenses.